POS1446 VARIATION IN SYSTEMIC DISEASE ACTIVITY MEASURED WITH ESSDAI IN A PROSPECTIVE LONGITUDINAL COHORT OF PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME WITHOUT IMMUNOSUPPRESSIVE TREATMENT
Authors: L. De Wolff, G. M. Verstappen, A. J. Stel, G. S. Van Zuiden, J. F. Van Nimwegen, A. Vissink, F. G. M. Kroese, S. Arends, H. Bootsma
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) has been used as primary endpoint in many recent randomised clinical trials (RCTs) in patients with primary Sjögren's syndrome (pSS). In multiple RCTs, a large placebo effect (&gt;50%) was observed with the ESSDAI. Since patients are often included with a moderate or high disease activity (ESSDAI ≥5), this placebo effect may partly be due to regression to the mean <sup>[1]</sup>. Little data is available on the natural course of the ESSDAI in patients who are not treated with immunosuppressives in daily clinical practice. <h3>Objectives</h3> To assess the variation in ESSDAI up to five years of follow-up in a cohort of pSS patients without immunosuppressive treatment. <h3>Methods</h3> This prospective longitudinal study included consecutive outpatients with pSS from the ongoing Registry of Sjögren Syndrome LongiTudinal (RESULT) cohort who fulfilled the ACR/EULAR classification criteria for pSS and who reached at least two years of follow-up with available ESSDAI until December 2022. Patients who received immunosuppressive treatment (biological DMARDs, conventional synthetic DMARDs, including hydroxychloroquine, or prednisone) were excluded. Patients visited the outpatient clinic once a year, or on clinical indication more often, and at each visit the ESSDAI was recorded. All available visits from baseline up to five years of follow-up were used for analyses. For the analysis at group level, yearly visits were used, defined as the nearest available ESSDAI within a time frame of ±6 months from the yearly visit. For analyses at individual patient level, all available ESSDAI scores were used. The largest change (Δ) in ESSDAI was calculated for each patient by subtracting the lowest ESSDAI from the highest ESSDAI score during follow-up. <h3>Results</h3> In total, 247 pSS patients fulfilled ACR/EULAR classification criteria and reached at least two years of follow-up with available ESSDAI. Of these, 142 patients did not receive immunosuppressive treatment and were included. 126 (89%) of these patients were female, median age was 53 years (IQR 43-65), median disease duration was 6 years (IQR 2-10) and 122 (87%) were anti-SSA positive. Median ESSDAI at baseline was 3 (IQR 1-6) and 93 (67%) patients had a low disease activity according to ESSDAI (score&lt;5). At group level, ESSDAI remained stable during five-year follow-up (Figure 1A). At individual patient level, the ESSDAI varied in the majority of patients (Figure 1B). The median largest Δ (worsening or improvement) in ESSDAI was 4 (IQR 2-8, range 0-22). In total, 93 (65%) patients had a Δ of ≥3 points in ESSDAI, and 65 (46%) patients a Δ of ≥5 points at some point during follow-up. Of the 93 patients with an ESSDAI&lt;5 at baseline, 50 (54%) patients remained in a low disease activity state during follow-up (median follow-up 40 months). Of the 46 (89%) patients who had a moderate or high disease activity (ESSDAI≥5) at baseline, 41 (89%) improved to a low disease activity for at least one visit (Figure 1B) and 37 (80%) patients reached the previously defined minimal clinically important improvement of ≥3 points improvement at some point during follow-up compared to baseline. <h3>Conclusion</h3> In this prospective longitudinal cohort of pSS patients without immunosuppressive treatment, a large variation in ESSDAI was observed during follow-up in individual patients, despite the median ESSDAI scores remaining stable at group level. This study underlines that natural variation in systemic disease activity measured with ESSDAI should be taken into account when using ESSDAI as study endpoint. <h3>Reference</h3> [1]De Wolff et al., Clin Exp Rheum 2020;38 (suppl 126):283-290 <h3> Acknowledgements</h3> The RESULT cohort was supported by the Dutch Arthritis Society (15-1-303) and unrestricted research grants from Bristol-Myers Squibb (NCT02067910) and Novartis. Several authors of this publication are member of the European Reference Network ReCONNET. <h3>Disclosure of Interests</h3> Liseth de Wolff: None declared, Gwenny M. Verstappen Consultant of: ArgenX, Alja J. Stel: None declared, Greetje S. van Zuiden: None declared, Jolien F. van Nimwegen Speakers bureau: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Arjan Vissink Grant/research support from: Unrestricted research grants from Bristol-Myers Squibb and Roche, Frans G.M. Kroese Speakers bureau: Bristol-Myers Squibb, Roche, Janssen-Cilag, Consultant of: Unrestricted research grants of Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Suzanne Arends Consultant of: ArgenX and Novartis, Hendrika Bootsma Speakers bureau: Bristol-Myers Squibb and Novartis, Consultant of: Bristol-Myers Squibb, Roche, Novartis and Union Chimique Belge, Grant/research support from: Unrestricted research grants from Bristol-Myers Squibb, Roche and AstraZeneca.